Evidence map›Paper›PMID 31594917›Full record

ArticleTranslational psychiatry2019

Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants.

Chelsey Ju, Laura M Fiori, Raoul Belzeaux, Jean-Francois Theroux, Gary Gang Chen, Zahia Aouabed, Pierre Blier, Faranak Farzan, Benicio N Frey, Peter Giacobbe and 13 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  11. Multi-omics approaches to major psychiatric disorders.Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Chelsey JuDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Laura M FioriDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Raoul BelzeauxDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Jean-Francois TherouxDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Gary Gang ChenDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Zahia AouabedDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Pierre BlierUniversity of Ottawa Institute of Mental Health Research, Ottawa, K1Z 7K4, ON, Canada.
Faranak FarzanCentre for Addiction and Mental Health, Toronto, ON, M6J 1A8, Canada.
Benicio N FreyMood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University; Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, L8N 3K7, Canada.
Peter GiacobbeDepartment of Psychiatry, University Health Network, University of Toronto, Toronto, ON, M5T 2S8, Canada.
Raymond W LamDepartment of Psychiatry, University of British Columbia, Vancouver, BC, V6T 2A1, Canada.ORCID http://orcid.org/0000-0001-7142-4669
Francesco LeriDepartment of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
Glenda M MacQueenUniversity of Calgary Hotchkiss Brain Institute, Calgary, AB, T2N 1N4, Canada.
Roumen MilevProvidence Care Hospital, Kingston, ON, K7L 4×3, Canada.ORCID http://orcid.org/0000-0001-6884-171X
Daniel J MüllerCentre for Addiction and Mental Health, Toronto, ON, M6J 1A8, Canada.
Sagar V ParikhUniversity of Michigan, Ann Arbor, MI, 48109, USA.
Susan RotzingerDepartment of Psychiatry, University Health Network, University of Toronto, Toronto, ON, M5T 2S8, Canada.
Claudio N SoaresProvidence Care Hospital, Kingston, ON, K7L 4×3, Canada.
Rudolf UherMRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AF, UK.
Qingqin LiJanssen Research & Development, LLC, Pennington, NJ, USA.ORCID http://orcid.org/0000-0003-4182-4535
Jane A FosterDepartment of Psychiatry, University Health Network, University of Toronto, Toronto, ON, M5T 2S8, Canada.
Sidney H KennedyDepartment of Psychiatry, University Health Network, University of Toronto, Toronto, ON, M5T 2S8, Canada.
Gustavo TureckiDepartment of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada. gustavo.turecki@mcgill.ca.ORCID http://orcid.org/0000-0003-4075-2736

Funding

CIHR EGM141899CIHR FDN148374
6 · The paper itself

Abstract

Major depressive disorder (MDD) is primarily treated with antidepressants, yet many patients fail to respond adequately, and identifying antidepressant response biomarkers is thus of clinical significance. Some hypothesis-driven investigations of epigenetic markers for treatment response have been previously made, but genome-wide approaches remain unexplored. Healthy participants (n = 112) and MDD patients (n = 211) between 18-60 years old were recruited for an 8-week trial of escitalopram treatment. Responders and non-responders were identified using differential Montgomery-Åsberg Depression Rating Scale scores before and after treatment. Genome-wide DNA methylation and gene expression analyses were assessed using the Infinium MethylationEPIC Beadchip and HumanHT-12 v4 Expression Beadchip, respectively, on pre-treatment peripheral blood DNA and RNA samples. Differentially methylated positions (DMPs) located in regions of differentially expressed genes between responders (n = 82) and non-responders (n = 95) were identified, and technically validated using a targeted sequencing approach. Three DMPs located in the genes CHN2 (cg23687322, p = 0.00043 and cg06926818, p = 0.0014) and JAK2 (cg08339825, p = 0.00021) were the most significantly associated with mRNA expression changes and subsequently validated. Replication was then conducted with non-responders (n = 76) and responders (n = 71) in an external cohort that underwent a similar antidepressant trial. One CHN2 site (cg06926818; p = 0.03) was successfully replicated. Our findings indicate that differential methylation at CpG sites upstream of the CHN2 and JAK2 TSS regions are possible peripheral predictors of antidepressant treatment response. Future studies can provide further insight on robustness of our candidate biomarkers, and greater characterization of functional components.

Indexed as

DNA MethylationAdolescentAdultAntidepressive AgentsCanadaCase-Control StudiesChimerin ProteinsCitalopramCpG IslandsFemaleGenome-Wide Association StudyHumansJanus Kinase 2Linear ModelsMajor Depressive DisorderMaleAntidepressive Agentschimaerin-beta3 protein, humanChimerin ProteinsCitalopramJAK2 protein, humanJanus Kinase 2

Identifiers

PMID31594917
PMCPMC6783543

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.